Mycoplasmas and ureaplasmas colonize the female genital tract of many animal species, including man. Without a doubt, in certain animals they produce disease in all segments of the tract, resulting in partial or total loss of fertility. However, uncertainty exists regarding their role in genital disease of man. Recently we have characterized a naturally occurring genital mycoplasmosis of rats and established a highly reproducible experimental model closely simulating the natural disease. The major objectives of the present proposal are: (1) to conclusively define the role of genital mycoplasmas in human infertility by an intensive cultural study of the upper and lower genital tract of infertile males and females and serological study of the organisms recovered, (all previous studies have been restricted to the lower tract with pathogenic mechanisms involved in the induction of infertility with emphasis on subtle mycoplasma-host interactions. This network can be revealed and disentangled only through the comprehensive application of pathological, microbiological, immunological, and endocrinological techniques; this involved interdisciplinary approach offers the only hope of accurately comprehending the role of mycoplasma, or any other infectious agent, in human infertility.